This invention is generally in the area of organic polymer chemistry, specifically multifunctional polymers.
Cell adhesion plays an important role in human disease. These interactions proceed by the interaction of receptors upon the surface of a cell with proteins or glycosaminoglycans upon the surface of another cell or within the extracellular matrix. These receptors may be proteins or glycosaminoglycans.
Routes to the interruption of these interactions typically involve competitive inhibition of these receptor-ligand interactions, for example, with antibodies (e.g., anti-glycoprotein IIb/IIIa complex for anti-platelet therapy), soluble ligands which act as receptor antagonists (e.g., cyclic RGD peptides or von Willebrand factor fragments), soluble receptors, or other competitors.
It has also recently been demonstrated that it is possible to inhibit these interactions by mechanical means, for example, by photopolymerizing poly(ethylene glycol)-based hydrogels upon the cell, cell aggregate, matrix or tissue.
An example of the use of hydrogels to inhibit tissue adhesion is described by U.S. Pat. No. 5,126,141 to Henry. The process utilizes thermo-reversible gels of mixtures of polyoxyalkylene polymers and ionic polysaccharides applied to the tissues as liquids.
Unfortunately, the inhibitor based methods have a disadvantage common to many drug therapies, in that it is difficult to restrict the activity of the inhibitors to the region of interest. Hydrogel barriers are difficult to place and it is difficult to control chemical processes associated with them.
Isolated cells or tissues have also been protected from cell--cell contact, in this case from attack by immune cells, by placement within microcapsules formed of water soluble non-ionic polymers such as polyethylene oxide grafted to polycationic polymers such as poly-L-lysine. However, this is restricted to the use of isolated cells or tissues which are encapsulated within the polymer at the time of polymerization for subsequent implantation into the body.
It is therefore an object of the present invention to provide methods for making and using compositions, and the resulting compositions, for inhibiting tissue adhesion and cell--cell contact within the body.
It is a further object of the present invention to provide methods for making multifunctional polymeric materials which can be biodegradable and which can be used for drug delivery, either at a specific tissue-polymeric material interface or as a result of release of bioactive agents during degradation of polymeric material.